New model predicts metabolic response to metals

Chalmers University of Technology

​Metal ions, for example iron, are vital to many cellular functions in all organisms. Researchers at Chalmers University of Technology have now developed a mathematical model to identify the role of metal ions in baker’s yeast. This model can be used to optimise industrial yeast strains producing a variety of bioproducts, or to design new diet supplements. ​

​Baker’s yeast, Saccharomyces cerevisiae, is used as a model organism for human cells and different cellular systems, such as metabolism. But the microorganisms can also be used as so-called cell factories, for sustainable industrial production where renewable sources are turned into different bioproducts, such as bioethanol, drugs, and chemicals. Knowledge about the metabolism is used to optimise the production rate and viability of the yeast cell factories, through genetic editing and by providing the best growth conditions.

Predict metabolic respons to reduced availability of metals

Metal ions play an important role in metabolism by serving as cofactors, helper molecules, to numerous metabolic enzymes, such as respiration but also many enzymes playing a role in detoxification. Although many enzymes have been reported to interact with metal ions, the quantitative relationships between metal ions, and metabolism, are lacking.

Photo of Yu Chen“We generated a model by applying the framework to Saccharomyces cerevisiae. The model showed good performance in terms of predicting intracellular metal ion abundances and predicting metabolic responses upon reduced availability of metal ions”, says Yu Chen, postdoc at the Department of Biology and Biological Engineering and first author of the scientific publication​ recently published in PNAS.

Iron deficiency leads to resource allocation

The research group also investigated the role of iron in metabolism and found that the model captured resource re-allocation upon iron deficiency. This suggests that yeast allocates iron based on optimisation principles. This means that yeast aims to always ensure allocation of iron to enzymes engaged in biosynthesis of amino acids that essential for cell growth.

In addition, the researchers validated one of the model predictions experimentally in the field of metabolic engineering.

These experiments showed that insufficient supply of iron could limit biosynthesis of p-coumaric acid, a chemical of great commercial interest used for production of dyes and polymers that are used in many materials, which relies on an iron-containing enzyme.

“Improve cell factories and diets”

“We believe that our model can be used to guide improvement of yeast cell factories and optimisation of growth conditions. More importantly, the framework can be easily applied to study metal ions within human metabolism, which can hopefully aid in explaining mineral deficiency and designing diets,” says Yu Chen.

Text: Susanne Nilsson Lindh

Read the scientific article in PNAS: Yeast optimizes metal utilization based on metabolic network and enzyme kinetics

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